Lethal and sublethal effects of phthalate diesters in Silurana tropicalis larvae

Abstract

Phthalates are compounds used in polymers to increase their flexibility and are now ubiquitous in the environment as a result of widespread use. Because few studies have focused on the adverse effects of these chemicals in aquatic species, the present study aimed to determine the effects of phthalate diesters in amphibians. Western clawed frog (Silurana tropicalis) tadpoles were acutely exposed to water spiked with monomethyl phthalate (MMP; 1.3-1595.5 mg/L), dimethyl phthalate (DMP; 0.03-924.0 mg/L), or dicyclohexyl phthalate (DCHP; 0.3-99.3 mg/L). Because few studies have addressed the toxicity of these specific phthalates in most organisms, the present study used higher concentrations of these chemicals to determine their toxicity pathways in amphibians and at the same time investigate a suite of genes known to be altered by the well-studied phthalates. Both DMP and DCHP increased larval mortality (9.1-924.0 mg/L DMP and 4.1-99.3 mg/L DCHP), increased frequency of malformations in tadpoles (0.1-34.1 mg/L DMP and 4.1-19.0 mg/L DCHP), and up-regulated cellular stress-related messenger-RNA (mRNA) levels (4.1 mg/L DCHP). To characterize the molecular toxicity pathway of these phthalates in tadpoles, transcriptome analysis was conducted using a custom microarray. Parametric analysis of gene set enrichment revealed important changes in the expression of genes related to drug metabolism and transport, liver metabolism, xenobiotic clearance, and xenobiotic metabolism after DMP and DCHP treatments, although these responses were less pronounced with MMP (the metabolite of DMP). The present study is one of the few studies that demonstrated complementarity between gene expression analysis and organismal effects. Environ Toxicol Chem 2016;35:2511-2522. © 2016 SETAC.

Phthalates modulate steroid 5-reductase transcripts in the Western clawed frog embryo

“…Moreover, prenatal exposure to DBP in rats significantly decreased Srd5α2 protein expression in the proximal penis (Kim et al, 2010). In contrast, MMP, DMP, and DCHP did not alter srd5α2 mRNA level in S. tropicalis (Mathieu-Denoncourt et al, 2016). These results suggest that the chemical nature of the phthalates as well as the developmental stage or tissue are important as to how the specific compound interferes with the level of certain genes/proteins.…”

“…For example, mRNA levels of cyp19, the enzyme responsible to aromatize T to estradiol, decreased in rodent cell lines when treated with MEHP and DEHP (Lovekamp and Davis, 2001;. In contrast, in amphibians, exposure to DCHP during embryogenesis in the Western Clawed frog increased cyp19 mRNA level; however, DMP and its metabolite, MMP did not alter cyp19 expression in the same species (Mathieu-Denoncourt et al, 2016). The later study is similar to the data found in this study as none of DEHP, DBP, or DEP modulated the expression of estrogen-related genes, such as cyp19, and erα.…”

“…For example, exposure to DBP and DEP at concentrations exceeding 500 µg/L significantly increased malformations, including abnormal gut coiling, cardiac abnormalities, and malformed faces, eyes, and brains in X. laevis (Bantle et al, 1999;Gardner et al, 2016). Furthermore, S. tropicalis exposed to dimethyl phthalate (DMP) and dicyclohexyl phthalate (DCHP) also resulted in malformations, such as edemas, improperly developed hearts, tail abnormalities, improperly coiled guts, and/or absent gills (Mathieu-Denoncourt et al, 2016).…”

“…In the present study, the lowest DBP and DEP concentrations significantly decreased mRNA levels of hsp70. In contrary, 1000 µg/L butyl benzyl phthalate (BBP) and DEHP induced hsp70 mRNA levels in Chironomus riparius larvae (Planelló et al, 2011) and exposure of S. tropicalis larvae to DCHP also increased hsp70 mRNA levels (Mathieu-Denoncourt et al, 2016). Cellular oxidative stress is caused by the presence of reactive oxygen species, which can lead to DNA damage in cells.…”

Effects of Dimethyl Phthalate (DMP) on Serum Sex Hormone Levels and Apoptosis in C57 Female Mice

“…DMP has a fatal effect on frog embryos. The DMP level increase leads to a significant rise in the malformation rate from 22.8% to 97.4% (10). At present, the influence and mechanism of DMP on the reproductive system is not clear, as no studies have been conducted on the effects of DMP exposure to the reproductive system.…”